This project is concerned with the characterization of the factors which participate in the control of salt excretion by the mammalian kidney. Because anesthesia often interferes with renal sodium handling, much of the present project is being done in conscious animals. Particular attention is being directed towards the role that plasma sodium concentration has in the regulation of urinary sodium excretion. Work on defining the mechanism responsible for the exaggerated natriuresis observed following hypertonic sodium chloride infusion, which increases plasma sodium concentration by 4-6 mEq/L, is focusing on elucidating the mechanism causing the inhibition of aldosterone secretion. This inhibition has been shown not to be due to either a decrease in plasma renin activity or in plasma potassium concentration. We have also been evaluating various sites within the body which might sense changes in plasma sodium concentration and consequently alter urinary sodium excretion. At present, we are investigating the GI tract in both dogs and rabbits, but to date we can find no evidence that the GI tract acts as a sensor for plasma sodium concentration. Work is also being directed towards determining if changing the sodium concentration of blood perfusing various areas of the CNS will alter urinary sodium excretion. An additional area of work is a quantitative evaluation of the effects that alteration in plasma sodium concentration have on the distribution of fluid between interstitial and plasma compartment.